Project description
Clarify the centriole’s role in sperm cells
Sperm cells contain two centrioles that are essential for fertilisation. Infertility rates are rising, with Assisted Reproductive Technology (ART) success at 30-40 %. Meanwhile, the majority of male infertility cases are unexplained, highlighting the need to understand sperm biology better. With the support of the Marie Skłodowska-Curie Actions programme, the CRiMI project will use advanced technologies, including cryo-electron tomography and single-particle cryo-electron microscopy, to study sperm cells and their centrioles. It will determine the structure of the proximal centriole and compare the ultrastructure in sperm from fertile and infertile individuals. The project will also clarify the role of centrioles in sperm cells, identify associated proteins, and enhance our understanding of male infertility.
Objective
Applying cutting-edge technology like cryo-electron tomography, subtomogram averaging and single-particle cryo-electron microscopy to sperm cells, I aim to uncover structural details of sperm centrioles.
As most other cells in the human body, sperm cells carry two centrioles called the proximal and the distal centriole. In the field of reproduction biology, it is widely accepted that these organelles are essential for the process of fertilization. One of their many important functions for this process is to provide centrioles for the zygote, as oocytes lose their own centrioles during maturation. Yet, the molecular mechanisms that determine their exact role in mediating fertility is not entirely understood.
Concurrently, infertility is increasing globally and so is the demand for treatment, commonly summarized as Assisted Reproductive Technology (ART). The success rate of ART is, however, only between 30-40% and even lower for women older than 35. One of the underlying reasons is that in up to 60% of the cases, male infertility is idiopathic. These numbers underpin the urge of improving our understanding of sperm biology and the molecular mechanisms of fertilization. This project defines three main objectives to achieve this:
1. Resolve the ultrastructure of sperm centrioles by applying cryo-electron tomography.
2. Isolation and high-resolution structure determination of the proximal centriole by cryo-electron microscopy.
3. Comparison of the centriole ultrastructure of sperm from fertile and infertile individuals.
A comprehensive structure-function investigation in a native setting will shed light on how centrioles are embedded within the neck of sperm cells. At high resolution, proteins that are associated to the centrioles and link them to surrounding structures can be identified. Finally, these findings will improve the understanding of male infertility, the diagnosis of such and ultimately increase the success rate of in vitro fertilization treatments.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- medical and health sciences clinical medicine andrology
- natural sciences biological sciences biochemistry biomolecules proteins
- natural sciences biological sciences cell biology
- social sciences sociology demography fertility
- natural sciences physical sciences optics microscopy
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Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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Call for proposal
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(opens in new window) HORIZON-MSCA-2023-PF-01
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3584 CS Utrecht
Netherlands
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